title: Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease.
abstract: Fibroblast growth factor 23 (FGF23) regulates phosphorus metabolism and is a strong predictor of mortality in dialysis patients. FGF23 is thought to be an early biomarker of disordered phosphorus metabolism in the initial stages of chronic kidney disease (CKD). We measured FGF23 in baseline samples from 3879 patients in the Chronic Renal Insufficiency Cohort study, which is a diverse cohort of patients with CKD stage 2-4. Mean serum phosphate and median parathyroid hormone (PTH) levels were in the normal range, but median FGF23 was markedly greater than in healthy populations, and increased significantly with decreasing estimated glomerular filtration rate (eGFR). High levels of FGF23, defined as being above 100 RU/ml, were more common than secondary hyperparathyroidism and hyperphosphatemia in all strata of eGFR. The threshold of eGFR at which the slope of FGF23 increased was significantly higher than the corresponding threshold for PTH based on non-overlapping 95% confidence intervals. Thus, increased FGF23 is a common manifestation of CKD that develops earlier than increased phosphate or PTH. Hence, FGF23 measurements may be a sensitive early biomarker of disordered phosphorus metabolism in patients with CKD and normal serum phosphate levels.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Isakova
authors.forename: Patricia
authors.initials: P
authors.lastname: Wahl
authors.forename: Gabriela S
authors.initials: GS
authors.lastname: Vargas
authors.forename: Orlando M
authors.initials: OM
authors.lastname: Gutiérrez
authors.forename: Julia
authors.initials: J
authors.lastname: Scialla
authors.forename: Huiliang
authors.initials: H
authors.lastname: Xie
authors.forename: Dina
authors.initials: D
authors.lastname: Appleby
authors.forename: Lisa
authors.initials: L
authors.lastname: Nessel
authors.forename: Keith
authors.initials: K
authors.lastname: Bellovich
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Lee
authors.initials: L
authors.lastname: Hamm
authors.forename: Crystal
authors.initials: C
authors.lastname: Gadegbeku
authors.forename: Edward
authors.initials: E
authors.lastname: Horwitz
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Townsend
authors.forename: Cheryl A M
authors.initials: CA
authors.lastname: Anderson
authors.forename: James P
authors.initials: JP
authors.lastname: Lash
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hsu
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000652:urine; D054559:Hyperphosphatemia / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000652:urine; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D010710:Phosphates / Q000097:blood* / Q000652:urine; D016226:Phosphorus, Dietary / Q000378:metabolism; D011237:Predictive Value of Tests; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology / Q000652:urine; D012720:Severity of Illness Index; D013997:Time Factors; D014481:United States; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; C470125:PTH protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D016226:Phosphorus, Dietary; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23